Those issues (adverse events, off-label discussions, fair balance presentation, no meaningful FDA guidance) hardly need rehashing here, and despite the barriers, progress has been made on the digital front, as evidenced by – if nothing else – pharma’s willingness to invest in smaller-scale social media efforts not directly tied to product sales. In the digital sphere, ROI means “hitting the primary endpoint,” and that endpoint could be data collection, engagement with widgets or functionalities on a page or within an app, or the number of visitors (or likes) on a Facebook page. “The ROI of social media is that your business will still exist in five years,” a quote from Socialnomics author Erik Qualman that surfaced in one of the presentations, speaks to the accepted necessity – in some quarters – of social media participation and customer engagement.

“Advertising has already largely shifted to what people say about your brand,” as opposed to the magazine, television and radio ads that people consume, said Martin Husar, customer strategy and innovation at Sanofi Canada. In Canada, DTC isn’t allowed, but last October Sanofi tapped the Toronto-based agency MediResource for an interactive Facebook campaign around atrial fibrillation (A-fib). The business objective, said Husar, was to “own the primary venues for Canadian patients and caregivers to learn about AFib.” By his measure, the company’s Afib at Heart | La fibrillation auriculaire à coeur Facebook campaign has been a success – one need not “like” the page to access the content, and thousands have clicked on tabs like “Ask the Expert,” or “Don’t Skip a Beat,” a Simon-inspired memory game.

A Janssen Canada educational campaign around psoriasis goes a step further, offering a list of available treatments, and a dermatology locator that returns only those dermatologists who “agree that they will use biologics” – Janssen markets Stelara, an immunomodulating biologic – and who have voluntarily signed up to be listed on Janssen’s Living Well With Psoriasis website, according to Spilios Asimakopoulos, director of marketing technology, Janssen Pharmaceuticals Canada. The site also offers a shareable psoriasis “severity calculator,” which is available online or as an app for download.

South of the Canadian border, others agree that the educational/disease awareness space is a good place for experimentation. John Patten, a sales rep for Facebook, told ePharma attendees that “Facebook makes sense in terms of initial support groups [for rare diseases], and locating others with the disease.” He also singled out Bayer’s Walk for Hemophilia and Sanofi Pasteur’s Voices of Meningitis as good examples of Facebook educational campaigns. “Pharma is more powerful in the unbranded, open wall pages” on Facebook, said Patten. Whitelisted brand pages, or pages with the comments function disabled, will be “de-prioritized in the news feed,” and they go against Facebook’s model, which Patten defined as “a distribution platform that promotes authentic sharing.” Perhaps as an added nudge to discourage whitelisted pages, Patten announced that by the end of February, “admins can drill down into individual commenters, and message them directly,” to help deal with “your drug turned my arm blue” adverse events comments.

A couple of hours before Patten’s presentation, however, a regulatory affairs director from a major pharmaceutical company was on a panel griping about the fact that while Facebook allows blocking of comments on the wall, “we can’t turn off sharing or commenting” on the actual brand image. Asked whether the company responds to such comments on the branded Facebook page, the panelist said no: “once you do that, where do you stop?”

Last week, FDA Commissioner Margaret A. Hamburg testified before the House Committee on Energy and Commerce, Subcommittee on Health to outline the agency’s case for supporting the fifth authorization of the Prescription Drug User Fee Act (PDUFA), also known as PDUFA V. In addition to offering her support for PDUFA V, Hamburg also discussed renewal of legislation for promoting pediatric drug testing, the need of FDA to invest in science and innovation, and the agency’s efforts in confronting the continual challenges of globalization. In tackling globalization, a basic question arises: does the United States face a pharmaceutical manufacturing disconnect?

In her testimony, Hamburg offered numbers to show the FDA’s record in reviewing applications for new drugs. In fiscal year 2011, FDA approved 35 new drugs, and almost 70% of these drugs were approved by FDA before any other regulatory agency, including the European Medicines Agency. Of 57 novel drugs approved by both FDA and the European Union between 2006 and 2010, 43, or 75%, were approved first in the United States. Preliminary data show that in 2011, over half of all new active drug substances were first launched in the US.

Although Hamburg offered these numbers to show the agency’s record in approving new drugs, they offer another important insight: namely, the US is an important source and market for drug innovation and pharmaceuticals. The US is the largest national market for pharmaceuticals, accounting for 36%, or $310.6 billion, of the $856 billion global pharmaceutical market in 2010, according to data from the IMS Institute for Healthcare Informatics. The top five EU markets (United Kingdom, France, Germany, Italy, and Spain) accounted for 17%, or $147.4 billion, in 2010. Emerging pharmaceutical markets, which include the BRIC countries (Brazil, Russia, India, and China) and 13 other emerging markets collectively accounted for $150.5 billion, or nearly 18%, of the global pharmaceutical market in 2010, according to IMS.

The data reveal the attractiveness of the US for launching new drugs and marketing existing drugs, but when it comes to manufacturing drug products or active ingredients, the US falls short. Approximately 40% of the drugs consumed in the US are manufactured outside the US, and up to 80% of the APIs in those drugs come from foreign sources, noted Hamburg in her testimony.

In her testimony, Hamburg outlined FDA’s efforts to deal with this increased globalization. In July 2011, FDA published a special report, “Pathway to Global Product Safety and Quality,”  a global strategy and action plan for the agency to more effectively oversee the safety of all products that reach US consumers. As detailed in the plan, over the next decade, FDA will focus on strengthened collaboration, improved information- sharing and gathering, data-driven risk analytics, and better allocation of resources through partnerships with counterpart regulatory agencies, other government entities, international organizations, and other key stakeholders, including industry.

Although these efforts by FDA are important and necessary from a public health and safety perspective, the underlying fundamentals engender a larger public policy question beyond the scope of FDA’s regulatory strategy. In a competitive global economy, what should the US be doing to encourage, cultivate, and retain domestic manufacturing of drug products and APIs? In this election year, debates over how to stimulate economic and employment growth are center stage, but what is noticeably absent is a focused plan to stimulate growth in the bio/pharmaceutical industry, a coveted source of high-technology, science-based innovation. That is one debate that is certainly worth having and one that hopefully will be had.

Allergan CEO David Pyott

Allergan CEO David Pyott is bullish on Botox’s potential as a salve for chronic migraine. He’s also betting on a next-gen dihydroergotamine (DHE) – Levadex – from MAP Pharmaceuticals.

It’s hard to know whether migraine sufferers will get behind Botox as a treatment; migraine patients are notoriously allergic to doctor visits, and many go undiagnosed. But for the worst kinds of migraines, particularly those that don’t respond to triptans or currently marketed DHEs, patients will probably be willing to try just about anything. Allergan CEO David Pyott, and MAP Pharmaceuticals CEO Tim Nelson, see headroom for growth in the category.

In 2009, the migraine market slipped into a steady decline after Imitrex, the go-to member of the triptan class, lost its patent (and blockbuster sales). Many of Imitrex’s classmates – Maxalt, Amerge, Zomig, and others – will face generic competition this year, if they aren’t facing it already. That makes Botox for migraine a difficult sell – it’s for chronic migraine, firstly, and it costs exponentially more than generic Imitrex – but during a 4Q earnings call yesterday Pyott said the migraine indication is performing “better than planned.” Around 4,600 physicians have been trained to give the injection, to date, said Pyott. “The vast majority of neurologists will inject for as long as three injection cycles,” even if they’re skeptical about the drug’s efficacy for migraine,” he Pyott. He’s hoping they’ll be convinced after that.

Branded print ads for Botox migraine will launch in women’s magazines this month, and an unbranded disease awareness campaign on television “has worked – the click-through on the website is positive,” said Pyott, adding that Allergan’s internal consumer surveys have shown “a high level of satisfaction” among patients.

After an upfront payment of $60 million last February, MAP Pharmaceuticals scored a $20 million milestone payment last August, when it filed Levadex with FDA. The company could receive up to $97 million more from Allergan if all goes well with the regulatory process; the PDUFA date on Levadex is March 26. Levadex, like Valeant Pharmaceuticals’ Migranal, is a DHE, but Migranal is a nasal spray, while Levadex is inhaled. The benefit with inhalation means that the drug sidesteps first pass metabolism en route to the brain – it avoids the GI tract, and potential dilution. At JP Morgan’s 30^th Annual Healthcare Conference in January, MAP CEO Tim Nelson said that Levadex “works faster, and has fewer side effects, than the triptans.” He added that 29 million scripts for migraine were written in 2008, and close to half of them were written off-label. After triptan, “41 percent of the scripts were for opioids, and 28 percent were anti-depressants,” said Nelson. MAP will hire 50 specialty sales reps if Levadex gets the FDA go-ahead, and will expand the drug into pediatrics and other neurological conditions later on, he said.

Levadex won’t compete directly with Botox for migraine; the former is for acute migraine, the latter for chronic migraine. Nelson said Allergan’s expertise in managed care, reimbursement and experience with FDA, makes it a good partner for Levadex. MAP is also looking for “a partner in Asia, and in ex-US in general,” said Nelson.

At $40 to $80, with a ceiling at $100 per dose, though, Levadex may be as tough a sell as Botox. But then again, migraine sufferers only want one thing when the pain sets in: for it to be gone.

By Lisa Henderson, Editor-in-Chief, Applied Clinical Trials.

In December 2011, the President’s Bioethics Commission released its “Moral Science: Protecting Participants in Human Subjects Research“. The report was ordered by President Obama following an October 2010 revelation that the US Public Health Service supported unethical research in Guatemala from 1946 to 1948 that involved intentionally exposing thousands of Guatemalans to sexually transmitted diseases without their consent.

The Bioethics Commission was then tasked to oversee a thorough fact-finding investigation into the specifics of the studies, as well as assure that current rules for research participants protect people from harm or unethical treatment, domestically as well as internationally.

The final report, available at this link and specifies 14 changes to current practice to better protect research subjects, as well as how the government should improve the tracking its over 18 federal agencies that follow the common rule for research programs with taxpayer dollars.

So again, this is specifically for government-funded studies and you can read all the different arms that receive funds, including the CIA, but of course the largest is the NIH. One of the Commission recommendations is:

“…. each federal department or agency supporting research with human subjects maintain a core set of data for their research programs that includes the title and lead investigator of each project, the location of each study, and the amount appropriated for the research. Each office should aid the public in learning more about the government’s research efforts by developing or improving publicly available electronic systems or releasing information through a government-wide system. To support these efforts, the Commission suggested that the Office for Human Research Protections or another office should administer a central web-based portal that links to each individual department or agency system. In addition, the government should consider developing a unified federal research database, which may ultimately be more cost-effective and efficient.”

Is it me or does it not sound like the “central web-based portal” or the “unified federal research database” be clinicaltrials.gov?

While the Commission could not easily identify how many research participants were enrolled in federal research (and not all of this is drug/interventional studies), they rounded it off to about 50,000 people.

So in doing the math, I’m assuming there are well over 18 biopharmaceutical companies that are conducting privately-funded research and are required by law to input this information into the clinicaltrials.gov online web database. And when these many biopharma companies fail to comply with this rule, as many critics will publicly announce as often as possible, the biopharma industry suffers another public perception setback and a trust issue.

In the meantime, wouldn’t managing 18 separate departments be akin to managing 18 privately-funded entitites? Each with their own culture, set of employees and roles, data and technology practices, and require that it happen within a certain timeframe?

I think so. I don’t think there need be separate rules for protecting human subjects in research. Nor should there be separate ways to educate the public on how to better serve their health or medical understanding. It’s everybody’s problem, private and public.

If you ever wanted to know what health economists might do with a billion dollars, the Obama Administration’s  Patient-Centered Outcomes Research Institute [PCORI] is about to tell all:  not right down to the penny, but good enough.  The congressionally funded – but independent – group has just released a document outlining priorities that will fuel a flood of research grants by mid-year. Application of that research will carry a significant impact on the evidence stream that increasingly determines Big Pharma’s access to providers and patients.
An outgrowth of the 2009 economic stimulus package, PCORI has a key role in implementing Obama’s health reform legislation with a mandate to evaluate the “comparative clinical effectiveness” of a vast array of health interventions, from drugs, diagnostics and devices to structural programs geared to prevention or wellness.  Congress authorized $1.1 billion for this task, a figure that dwarfs what other countries currently spend on all forms of effectiveness research.  It follows that the PCORI priorities will carry influence outside the US.  And there is an even larger effect should PCORI end up enabling  research that industry has traditionally eschewed, such as head-to-head drug comparisons and broad, population-based observational studies.

PCORI’s Draft National Priorities for Research, unveiled on January 23, strikes a tentative tone.  It repeatedly states the document is unfinished, and the sub-head to the title refers to  the proposed research agenda as “version one.”  Much of the text is devoted to how PCORI intends to consult widely with a broad array of stakeholders – led by patients, care-givers and their representatives – prior to final action by the group’s governing Board, probably in April.  PCORI staff will initiate the outreach through private meetings and focus groups, but there is also an all-day, open-to-the-public consultation scheduled for February 27 near the PCORI headquarters in Washington.  The comment period on the draft continues to March 15.

The five priorities set forward in the document are also very broad and will likely be read differently by different stakeholders.  The first, comparative assessment of prevention, diagnosis and treatment options, is arguably the most important. In fact, PCORI intends to devote 40 per cent of its time and resources to this area.  The goal here is research to evaluate alternatives to designate those products and practices that produce superior patient outcomes.  Although cost is not an intended path of inquiry, PCORI does have the right under law to fix priorities that take into account “the effect on national health expenditures associated with a health care treatment.”  Hence there is some risk that activities under this priority, which focuses on new technology and product interventions, could range further afield than clinical aspects alone.

Ranking behind this are two priorities that will take another 40 per cent of the PCORI budget:  improving health care systems; and accelerating patient-centered methodological research.  In the first case, this entails examining changes in health services and infrastructure, including the impact on efficiency of changes in the way these services are delivered, and by whom.  The research in methodologies priority will support work to improve the quality and usefulness of clinical data, as well as developing standards for new forms of research like patient registries, observational studies and meta-analyses.   It is hoped these new standards will promote better decision-making around rare diseases – where, it should be noted, current treatments are quite costly, with drugs leading the way.

Some 20 per cent of resources will be spent around the two final priorities:  investigating health disparities; and communication and dissemination. The disparities agenda is politically popular and focuses on revealing areas of implicit bias in the health system, from gender and race to age and social parameters, where practice patterns differ and outcomes can suffer because of them.  Expect from this an upswing in attention to the social determinants of health.  The latter priority is geared to raising patient compliance rates with treatment, improving patient understanding of options they have in treatment and promoting better patient-clinician communication, and evaluating the promise and success of electronic health records and other new information technologies.

The patient interest is the common thread running through each priority.  Patient representatives will not only be formally consulted as specific projects are developed, they will serve on in-progress review committees and will be asked weigh in on results.

Word to the Wise..
While PCORI has taken pains to consult and to avoid stepping into the minefield of cost and “value,” industry has good reason to be wary as its ambitious work plan moves forward.   The high level of inclusiveness given to the patient community may end up politicizing the process and interfere with the integrity and robustness of the research protocols. Raising this is prudent given the level of aggressiveness that patient advocates show in rallying support for their disease.   Even with a billion dollars to spend, prioritization means that while some will be let in, others will be left out.  The temptation will be for some groups to ask Congress to intercede – few scientists or researchers, of any stripe, want that.

Likewise, PCORI’s interpretative skills will be tested if it proceeds with proposals to  “synthesize” existing studies to “create a more cohesive body of evidence.”  There will invariably be disagreements in rendering judgments from different studies and it entails the risk that important clinical decisions will proceed without acknowledgment of methodological gaps and important disease variations in the populations under study.  In fact, PCORI funding for more meta analyses in place of clinical trials raises questions of encouraging population bias, particularly as the technological capacity to expand the data set to millions of people becomes commonplace.   PCORI’s Methodological Committee has not publicly weighed in on this yet, but when it does the discussion is bound to be controversial.

In a country where mere mention of the word “rationing” spawns howls of protest, PCORI is probably right in framing any document it publishes in the vaguest possible terms.  But this may in time damage its effectiveness in facilitating superior health outcomes.  I ask:  can an organization that calls itself “patient centric” still be scientifically pure and empathy free?  In the messy politics of health care, isn’t that the same as being  tone deaf?

PCORI’s online survey to gauge reaction to the strategy document can be accessed here.

A magazine ad for Boniva, fronted by actor Sally Field, generated the DDMAC (now the Office of Prescription Drug Promotion, or OPDP) Untitled Letter last year due to following phrase: “After one year on Boniva, 9 out of 10 women stopped and reversed their bone loss.” That didn’t jibe with the scientific data, DDMAC said in the letter, before requesting that all ads containing the phrase be removed from the campaign.

Genentech went a step further. In September of last year, the company began running corrective magazine ads addressing the overstated claim. The corrective ad states that the violative ad “may have given you the wrong impression.” It goes on to state that “Boniva has not been proven to stop and reverse bone loss in 9 out of 10 women and is not a cure for postmenopausal osteoporosis.” The corrective ads will run though April 2012.

Unlike their mild-mannered, Untitled Letter cousins, Warning Letters are considered more severe, and they typically mandate corrective ads to clear up any overstated claims or minimized risk information. Given that Genentech received the former communique and not the latter, it’s notable that the company chose to run corrective ads without a mandate.

After speaking with DDMAC about the Untitled Letter, Genentech worked with the agency to create and then “voluntarily” launch the corrective ads last September, according to Chris Vancheri, director, public affairs, at Genentech.

In a statement, Genentech said that in addition to the corrective advertisements – which are running in several women’s magazines, including Weight Watchers and this month’s WebMD the Magazine – “our clinical specialists have reached out to health care providers” to inform them about the corrective ads, which intend to “clarify the benefits and risks of Boniva in women suffering from post-menopausal osteoporosis.”

Sally Field was the face of Boniva beginning in 2006, but Vancheri says Field is “no longer engaged” on the campaign. GlaxoSmithKline signed a co-promotion deal with Roche on Boniva in 2001, but the companies broke the partnership in 2010.

In response to off-label inquiries about a drug, biopharma companies can use the kind of boilerplate they’ve been inserting on social media sites for years – thanks for your comment, here’s our contact information, call us for more information – but they cannot address the question publicly, where it appears, a privilege many hoped would be included in FDA’s long-promised and long-awaited social media guidelines. Companies must also include a “mechanism for providing readily accessible current FDA-required labeling,” but cannot include a link to anything that could be construed as promotional, like a “product website, product promotional materials, firm websites, or third-party websites.” Guidance on responding to unsolicited requests for off-label information was published in the Federal Register a few days before the end of 2011.

Responding to an unsolicited off-label question/comment is only appropriate when a specific brand is named, and if the question is “broad in nature,” drug companies should “appropriately narrow the question.” FDA recognizes the fact that companies are “capable of responding to requests about their own products in a truthful, non-misleading, and accurate manner,” and that companies probably know more about their own products than other self-appointed responders:

It can be in the best interest of public health for a firm to respond to unsolicited requests for information about off-label uses of the firm’s products that are made in public forums, especially since other responders may not provide or have access to the most accurate and up-to-date medical product information.

Unlike other forum responders, who can comment publicly in response to any question, manufacturers must wait for the original commenter to respond to the boilerplate message with contact information, before providing “any substantive communication about off-label uses for the product, in response to the original unsolicited off-label question,” and that communication must occur “solely between the firm and the individual who made the request…the firm should not make its detailed response with off-label information publicly available within the same forum.”

FDA’s guidance on industries’ social media interaction with patients, at least with respect to off-label inquiries, seems to be: Don’t participate publicly. According to the guidance document, this sentiment reflects a concern that publicly posted off-label information – in response to an unsolicited query – would be available for an indefinite period of time, and would also reach the eyes of readers who have not requested such information. Even if the drug information is accurate when it’s posted, it may not be accurate next month. For viewers who didn’t ask about an off-label use, but are still party to a public response, the information itself, regardless of its scientific merit, “may promote a product for a use or condition for which FDA has not approved or cleared.”

Those companies that would like to respond to an individual with a question, assuming that person has called or emailed the company in response to the provision of contact information – contact info that leads to a firm’s medical or scientific department, not a marketing department, the guidance clearly states – should include the following materials, according to the document:

• FDA—required drug label
• A prominent statement saying the product has not been FDA approved
• A prominent statement disclosing approved indications, if any
• A prominent statement of all important safety info, including box warnings, if any
• A complete list of references for all of the information disseminated in the response (firms should use peer-reviewed articles whenever possible)

Companies should also maintain the following records about off-label responses:

• The nature of the request for information, including the name, address and affiliation of the requestor
• Records regarding the information provided to the requestor
• Any follow-up inquires or questions from the requestor

The guidance is open for comment for 90 days. Here’s the Federal Register entry.

In little more than two years, the main elements of the HCR will take hold across the nation.  As implementation continues to ramp up, one of the more intriguing questions surrounding its activation is, is the “S” word being realized?…That is, “S” as in “savings.” Are the much publicized “savings” that were projected in early 2010 actually occurring as we head towards January 1, 2014?

The savings, according to the final 2010 CBO estimate, would provide a “net reduction in federal deficits of $143 billion…over the 2010–2019 period as result of changes in direct spending and revenues.”

Further, in August 2010, an NEJM article co-authored by Peter Orzag and Ezekiel Emanuel, MD, estimated that by 2030, total HCR savings would be up to $1 trillion.

Now, however, as various HCR elements meet the real world, many of the “savings” have proved illusory, if not completely unachievable.

To illustrate these difficulties, let’s take a look at the current status of “savings” in three key programs — Medicare Advantage, the CLASS Act, and ACOs.

Medicare Advantage

Most of us know the story of Medicare Advantage (MA).  Initially designed in the ‘90’s to provide managed care services in rural areas, the program was tapped by the Bush Administration to be dramatically expanded in 2003 under the Medicare Modernization Act.

However, because of higher premiums paid under the “new” MA, the program became a target of Congressional Democrats during the HCR debate. In the end, $136 billion of the $500 billion needed to start HCR’s expanded Medicaid program was sliced out of MA and credited as a “savings” in the final law.

All was well until last January when the first real “extractions” from MA services were scheduled to take hold.  Interestingly, the designated cuts didn’t occur.  In April, USA Today reported that rather than cutting MA premiums, HHS was actually “enhancing” them. Further, as pointed out by Kaiser Health News, more patients were signing up:

Despite predictions that last year’s healthcare law would doom Medicare’s private insurance plans, it’s not happening – at least not yet.  Enrollment in Medicare Advantage plans continues to grow at a brisk pace…

So, MA certainly doesn’t seem like a program scheduled for significant cuts by January of 2014.  And the projected CBO “savings” for HCR?  The “S” word for MA isn’t being discussed by HHS.

ACOs

The concept of the accountable care organizations (ACOs), from the start, was predicated on projected “savings” that were to be driven by this new concept.  As Families USA stated in September of 2010:

If the accountable care organization delivers high-quality care at lower costs…This new payment approach will create an estimated $5 billion in savings for the Medicare program (by 2019).

Sounds pretty good.  However, problems with the ACO concept surfaced soon after HHS issued the first rules in April of this year.  The pushback from providers was intense and focused on three key points of contention:

First, what was an ACO?  An HMO, a PPO, or some other new medical delivery variant?

Secondly, what about liability for losses under ACOs?  According to HHS, providers would be responsible for any losses that might occur under the program.  Insurers and hospitals plans rejected this as they saw ACOs as “experimental” and as such, very risky business propositions.

Thirdly, how would ACOs save money?  Of particular concern was one section of the concept that stated ACO patients were free to be seen by any doctor.  The providers said if ACOs were going to save money, they would need to control patient access to medical care.

After a lot of discussion, HHS withdrew the initial rules and issued a new set in October. The new rules addressed the questions about liability (there is none); and to a degree, further defined an ACO.

But on the question of direct “savings”, nothing was settled.  That’s because it appears HHS is still not willing to impose HMO-like closed panels on patients, so patients can get care wherever they wish. How do you control medical costs, and generate “savings”, if you have no access control over your patients?

So will ACOs and their projected “savings” start as scheduled on January 1, 2012?  Not clear.  Realistically, though, the “S” word in ACOs is very much in question.

CLASS ACT

The final HCR “savings” question is cut and dried…Of all the aspects of the law that has missed on projected “savings”, the CLASS Act is clearly at the top of the list.  Why?  Because the prospective long-term care program for seniors went kaput in October when HHS designated the plan as “unsustainable”.  So, for the CLASS ACT, the “S” word is not an issue.  A cool $86 billion in savings is off the table. If you’re counting, that’s nearly 10% of the total 20 year “savings” projected in the noted NEJM article.

Vanishing “Savings”

We can all wonder why the CBO-certified HCR “savings” asserted in 2010 have begun to vanish. Some of these occurrences, however, do seem explainable:

First, let’s take the most obvious case: The CLASS Act

From the beginning, the actuarial theory that drove the alleged “savings” in the program was flawed: in 2009, Rick Foster, the Medicare Actuary, said the “savings” projected in the CLASS Act were illusory. It took HHS until this fall to finally agree.  In the meantime, $86 billion in “savings” has evaporated. The worrisome question is, will we find out other parts of HCR are equally “unsustainable?”

Second, we need to acknowledge that politics has entered into this “savings” picture. In the case of Medicare Advantage, someone at HHS apparently awakened to the fact that on January 1, 2011 the Administration was scheduled to take MA benefits away from nearly 10 million senior citizens.  Not a wise thing to do with a national election coming in 2012.  Solution? Don’t reduce MA in 2011.  To my point on politics in the “savings” equation, do we expect the 2011 MA enhancements to continue after November 2012?  I’ll leave that to you to ponder.

As for ACOs, I think it’s a similar case.  The only way to realize savings in the new ACO concept is to lock people into a single physician, under a closed panel of services.  Why hasn’t HHS done this?  Because a lot of people really don’t like a closed panel approach to care. My guess is the $5 billion in “savings” scheduled to begin accruing in January 2012 will remain a mirage until after November of 2012.

So where do things stand with the “S” word in HCR as we close out 2011?  Right now, the evidence of actual “savings” is rather murky.  Taking just these three important programs (MA, CLASS, ACOs), and the approximate $225 billion of the projected 10 year “savings” they are designated to drive, we find their “savings” are either off the table completely, or, at best, appear to be suspended until we get by the November 2012 elections.  Given that, the Administration’s anticipated overall savings of $143 billion for the period 2010–2019 would have to be charitably labeled as “behind schedule.”

That’s my point of view.  I would like to have your thoughts on the “S” word in HCR.

On November 17, FDA’s Risk Communication Advisory Committee (RCAC) will convene to discuss the best ways to take a drug’s complex clinical data, and present it to doctors and patients in an understandable way. The stated goal is to improve healthcare decision-making by clinicians, patients and consumers.

At issue is the implementation of a drug facts box or table, which would appear in a drug’s promotional labeling and print advertising. Research shows that a drug facts box, or a “table quantifying [health] outcomes with and without a drug,” as described by Dartmouth Medical School profs Lisa Schwartz and Steven Woloshin, could do a better job presenting the benefits and risks of a particular medicine, which facilitates a more informed decision about treatment. It would also dramatically change the way drugs are currently promoted, at least in print. (For a facts box mock-up, click here)

Woloshin says he has not looked into broadcast media applications for the facts box, but suggests that certain warnings, such as approval on the basis of a surrogate outcome, or the main efficacy finding for a drug, could be easily inserted into broadcast spots. For broadcast, “we imagine the primary goal would be to point people to a drug [facts] box, either in print or online…we have not tested these ideas, but hope to in the future,” says Woloshin.

On facts boxes in print, however, Woloshin and his colleagues have conducted extensive research, and have published a substantial body of literature. In fact, three years ago, FDA’s RCAC – then chaired by Baruch Fischhoff, of Carnegie Mellon University – gave the facts box a unanimous recommendation. Speaking to PharmExec about the facts box, Fischhoff calls it “a sound design, both analytically and empirically…it follows the theories of risk communication, it has demonstrated efficacy in its field trials, and is clearly much better than what we have out now.”

So what’s the hold-up on implementation, you may be wondering. Unsubstantiated suspicions abound, and a request for comment from HHS – which received a mandate via the Patient Protection and Affordable Care Act (Section 3507) to review the evidence for or against a quantitative summary of a drug’s risk and benefit, “such as a table or drug facts box,” and to make a judgment – went unanswered. A report filed to Congress by HHS in March requested at least three more years for additional research.

“It’s crazy that people – doctors, patients, tax-payers – don’t have ready access to summaries of [a drug’s efficacy and risks] in a way that we’ve shown can help them make better decisions,” says Woloshin. “FDA is supposed to be interested in transparency, getting information out to people in the most transparent form; that’s exactly what the facts boxes are meant to do.” Asked about possible reasons for foot-dragging at HHS, Woloshin says he’s “completely baffled by the delay,” an opinion he made known in the editorial pages of the New York Times last July. Fischhoff agrees: “Given the amount of work that’s gone into the fact box and the evidence that supports it, it’s hard for me to believe that [alternate design studies conducted by HHS/FDA] would justify a delay of a couple of years.”

RCAC is unlikely to make any bold decisions on Thursday; the discussion is primarily geared toward whether or not substantial gaps exist in the literature around a standardized risk/benefit format, and if data exist to shed light on how to select and present information for clinicians, patients and consumers. Interested parties can sit in on the RCAC meeting remotely, here.

In an exhaustive review of the literature on using quantitative summaries for the presentation of drug benefit and risk information – published on August 15^th – FDA admits that “numeric presentation of risk/benefit information appears to have had a positive impact on several outcomes relative to non-numeric presentation,” (non-numeric presentation means using words like “often” or “rare,” in place of numeric statistics). But the report insists that important gaps exist in the literature, such as “insufficiently investigated actual behaviors” versus theoretical behaviors, and a “focus only on risk information rather than on both risk and benefit information.” The report also cites differences in “a person’s numeracy or literacy levels” as a point against standardized, quantitative summaries.

Note: Apologies for the lack of a facts box quiz, alluded to in PharmExec‘s weekly newsletter. The quiz unfortunately died from editorial and technical complications. -BC

FDA approved 35 innovative drugs in fiscal 2011, including treatments for hepatitis C, prostate cancer, Hodgkin’s lymphoma, and lupus. This number of approvals is among the highest in the past 10 years, and it reflects the agency’s efforts to hasten patients’ access to new drugs. In the past two years, the agency’s lower levels of approvals—21 drugs in 2010 and 25 in 2009—caused concern throughout the industry and in Congress. We may feel grateful to FDA, but we also should ask how the agency achieved this high number of approvals.

One technique was accelerated approval for drugs to treat serious diseases. This authority allows the agency to approve a drug based on clinical data showing that it is reasonably likely to have a clinical benefit, even if data do not demonstrate that the drug has this benefit. Almost half of the newly approved drugs received Priority Review because they had the potential to offer major advances in treatment, or because no adequate therapy existed. FDA sets a six-month target date to review such drugs.

Although these changes in procedure are well-intentioned, we may legitimately ask how they will affect patients’ safety. After all, GSK’s diabetes drug Avandia received fast-track approval, but an article published in The New England Journal of Medicine later linked the drug to an increased risk of heart attacks. The Wall Street Journal notes that a Senate Finance Committee report last year accused the company of hiding data showing Avandia’s cardiovascular risks, and GSK has just agreed to pay the US government $3 billion to settle this and other claims.

Creating a short timeline for drug approval could hurt the agency’s reviews of clinical data. FDA approved Pfizer’s smoking-cessation drug Chantix after an accelerated priority-review process. The agency concluded that the drug did not increase the risk of psychiatric problems such as depression. But researchers from Wake Forest Baptist Medical Center found that Chantix was eight times more likely to result in suicidal behavior or depression than nicotine-replacement products. One reason for the discrepancy could be that, unlike FDA, the researchers performed disproportionality analysis on the data—a technique that is increasingly being used to find links in side-effect data that normally escape detection in clinical trials.

FDA’s staff includes well-vetted and experienced scientists, but they need sufficient time to work thoughtfully and thoroughly. Even though the agency’s initiative has increased the number of new-drug approvals, it may also be increasing the risk that a company can hide negative data from regulators, or that the agency’s own analyses will not be as complete as they could be. In light of the problems with Avandia and the conflicting studies about Chantix, I think FDA should review its efforts to promote innovation to be sure that the agency maintains high standards for drug safety.

Erik Greb